SOCE Inhibitors and Therapeutic Uses Thereof

Abstract

The present invention provides SOCE inhibitors that are useful as therapeutic agents in a variety of applications. The present invention also relates to pharmaceutical compositions, products and kits comprising such SOCE inhibitors, and methods of using the SOCE inhibitors in the treatment of a variety of diseases.

1 - 14 . (canceled) 
     
     
         15 . An aromatic azole compound having chemical formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is one, two, three, four or five substituents, wherein each of the substituents is independently selected from H, OH, a halogen, NH 2 , an alkoxy, an aryloxy, OCH 2 OR, wherein R is an alkyl group, and O-THP, wherein THP is tetrahydropyranyl; 
         A is CH 2  or O; 
         if A is CH 2 , then n=0, 1 or 2, and if A is O, then n=2 or 3; 
         Z is O, NH, NHCO or CONH, NR, wherein R is an alkyl group, NHSO 2  or SO 2 NH; 
         X is one of the following groups: 
       
       
         
           
           
               
               
           
         
         wherein: 
         R 2  is H, Cl, Br or CF 3 ; 
         R 3  is one, two, three or four substituents, wherein each of the substituents is independently selected from H, OH, CF 3 , F, Cl, NH 2 , COOH, and CONH 2 ; 
         R 4  is one, two or three substituents, wherein each of the substituents is independently selected from H, F, CF 3  and an alkyl group; and 
         R 5  is one or two substituents, wherein each of the substituents is independently selected from H, F, and CF 3 , 
         or a pharmaceutically acceptable salt, solvate or hydrate thereof, or derivative thereof, or a prodrug thereof. 
       
     
     
         16 . The aromatic azole compound according to  claim 15 , wherein the aromatic azole compound has the chemical formula (II): 
       
         
           
           
               
               
           
         
       
     
     
         17 . The aromatic azole compound according to  claim 16 , wherein the aromatic azole compound has the chemical formula (III): 
       
         
           
           
               
               
           
         
       
     
     
         18 . The aromatic azole compound according to  claim 15 , wherein the aromatic azole compound has the chemical formula of one of the following compounds: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
     
     
         19 . The aromatic azole compound according to  claim 18 , wherein the aromatic azole compound has the chemical formula of one of compounds 6αc (DAD 4-546), 6αt (VAL 1-76), 6αm (VAL 1-77), 6αu (VAL 1-75), 6αv (VAL 1-64), 6αe (DAD 4-548), 6αd (DAD 4-547), 6αo (DAD 4-551), 6αp (DAD 4-552), 6αab (DAD 4-553), 6αac (DAD 4-566), 6αad (DAD 4-567), 6αad (DAD 4-568), 6αs (DAD 4-570), 6αae (DAD 4-569), 6αaa (DAD 3-473), 6αm (DAD 3-475), 6αn (DAD 3-474), 6αz (DAD 4-472), 6αb (DAD 4-573), 6αaa (DAD 4-574), and 6αab (DAD 4-575). 
     
     
         20 . The aromatic azole compound according to  claim 19 , wherein the aromatic azole compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
     
     
         21 . A pharmaceutical composition comprising an effective amount of at least one aromatic azole compound according to  claim 15 , and a pharmaceutically acceptable carrier or excipient. 
     
     
         22 . A method for treating a disease associated with SOCE dysregulation or dysfunction in a subject, the method comprising a step of administering to the subject a therapeutically effective amount of an aromatic azole compound according to  claim 15  or a pharmaceutical composition thereof. 
     
     
         23 . The method according to  claim 22 , wherein the disease associated with SOCE dysregulation or dysfunction is selected from the group consisting of inflammatory diseases, immunodeficiency diseases, autoimmune diseases, allergies, cardiovascular diseases, cardiorespiratory diseases, vascular diseases, neurodegenerative diseases, skeletal muscle diseases, thromboses, and cancers. 
     
     
         24 . The method according to  claim 23 , wherein the disease associated with SOCE dysregulation or dysfunction is selected from the group consisting of inflammatory bowel diseases, pancreatitis, rheumatoid arthritis, multiple sclerosis, asthma, psoriasis, and cancers.